Apparatuses for and methods of processing cells and related structures

Abstract

Apparatus for processing life-based organic particles, including particles selected from the list comprising cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos, comprises a hollow volume (10) that (a) is internally divided into at least first (14), second (16) and third (17) sub-volumes by at least two phaseguides (12, 13) formed inside the volume and (b) includes parts that are relatively upstream and relatively downstream when judged with reference to the movement of a meniscus or a bulk liquid in the volume (10). The apparatus includes at least first, second and third fluid conduits (19, 21, 22) connected to permit fluid communication between the upstream exterior of the volume (10) and a respective said sub-volume (14, 16, 17); and at least one further conduit (24) connected to permit fluid communication between the downstream exterior of the volume (10) and a said sub-volume. The first sub-volume (14) contains one or more life-based particles supported in or by a gel or gel-like substance; and the second sub-volume (16) communicates with the first sub-volume so as to permit transport of substances between the first and second sub-volumes (14, 16) and contains at least one gel or gel-like substance.

The invention claimed is: 
     
       1. A method of processing cells, cellular spheroids, tissues, eukaryotes, microorganisms, organs or embryos, the method comprising:
 a. charging a first sub-volume of an apparatus with a quantity of a gel or gel-like substance containing or supporting one or more cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos, 
 wherein the first sub-volume is a sub-volume of a volume of the apparatus internally divided into at least first, second, and third sub-volumes by at least two confining phaseguides formed inside the volume, 
 the apparatus including at least first, second and third fluid conduits connected to permit fluid communication between an upstream exterior of the volume and a respective said sub-volume and at least one further conduit connected to permit fluid communication between a downstream exterior of the volume and a said sub-volume; 
 b. permitting or causing gelation of the gel or gel-like substance; 
 c. charging at least the second sub-volume with a gel or gel-like substance; and 
 d. causing or permitting fluid communication between the first and second sub-volumes. 
 
     
     
       2. The method according to  claim 1 , wherein each of the at least two confining phaseguides is a protruding three-dimensional structure, or an area on an internal surface of a volume that is of a differing degree of wettability. 
     
     
       3. The method according to  claim 1 , wherein each of the at least two confining phaseguides spans the complete length, width, or height of the meniscus and represents a pressure barrier for advancement or recession of the meniscus. 
     
     
       4. The method according to  claim 1 , further comprising permitting transport of substances between the first and third sub-volumes, wherein the third sub-volume contains a perfusate. 
     
     
       5. The method according to  claim 2 , further comprising allowing the perfusate to flow inside the third sub-volume. 
     
     
       6. The method according to  claim 1 , wherein the second sub-volume contains one or more cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos supported in or by the gel or gel-like substance. 
     
     
       7. The method according to  claim 6 , wherein the one or more cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos in the second sub-volume differ from the one or more cells, cellular spheroids, tissues, eukaryotes, microorganisms, organs or embryos in the first sub-volume. 
     
     
       8. The method according to  claim 1 , wherein the apparatus comprises a third phaseguide defining a fourth sub-volume inside the volume. 
     
     
       9. The method according to  claim 8 , further comprising permitting transport of substances between the first and fourth sub-volumes and wherein the fourth sub-volume contains a perfusate. 
     
     
       10. The method according to  claim 9 , further comprising allowing the perfusate to flow inside the fourth sub-volume. 
     
     
       11. The method according to  claim 8 , wherein the fourth sub-volume contains a fluid substance the effect of which on one or more cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos in the first sub-volume is required to be investigated. 
     
     
       12. The method according to  claim 8 , wherein the third and fourth sub-volumes contain fluid substances that give rise to a concentration gradient in at least the first sub-volume. 
     
     
       13. The method according to  claim 12 , wherein the fluid substance is or includes a liquid or liquid-based substance. 
     
     
       14. The method according to  claim 8 , wherein the fourth sub-volume contains or is chargeable with a gas. 
     
     
       15. The method according to  claim 1 , further comprising stratifying the gel or gel-like substance using one or more phaseguides in at least the first sub-volume. 
     
     
       16. The method according to  claim 1 , further comprising controlling, with one or more further phaseguides, transmission of liquids or liquid-based substances to a further volume of the apparatus connected to at least the first fluid conduit. 
     
     
       17. The method according to  claim 16 , wherein controlling transmission of liquids or liquid-based substances comprises allowing any gel or gel-like substance in excess of a predetermined quantity of a gel or gel-like substance charged to the first sub-volume to enter the further sub-volume. 
     
     
       18. The method according to  claim 1 , further comprising maintaining a predetermined shape of a boundary of a gel or gel-like substance in at least the first sub-volume by including at least one contour phaseguide in the volume between the first and second sub-volumes. 
     
     
       19. A method of processing cells, cellular spheroids, tissues, eukaryotes, microorganisms, organs or embryos comprising the steps of:
 a. charging a first sub-volume of an apparatus with a quantity of a gel or gel-like substance containing or supporting one or more cells, cellular spheroids, tissues, eukaryotes, micro-organisms, organs or embryos, 
 wherein the first sub-volume is a sub-volume of a volume of the apparatus internally divided into at least first, second and third sub-volumes by at least two contour phaseguides formed inside the volume, 
 the apparatus including at least first, second and third fluid conduits connected to permit fluid communication between an upstream exterior of the volume and a respective said sub-volume, at least one further conduit connected to permit fluid communication between a downstream exterior of the volume and a said sub-volume; 
 b. charging at least the second sub-volume with a gel or gel-like substance; and 
 c. causing or permitting fluid communication between the first and second sub-volumes.